Introduction: Drug resistance has been a continuous challenge in cancer treatment. The use of nanotechnology in the development of new cancer drugs has potential. One of the extensively studied compounds is thymoquinone (TQ), and this work aims to compare two types of TQ-nanoformulation and its cytotoxicity toward resistant breast cancer cells. Read More

The explosion of stem cell research in the past several years has made its presence known in the field of cardiology and has been recently tasked with solving one of the largest health problems to afflict humanity: cardiovascular disease (CVD). Although stem cell therapy has shown glimmers of promise, significant problems remain that need to be addressed if these therapies are to ever find true success. One way to achieve this success is to take engineering principles and apply them to fabricate engineered cardiac tissues, composed of the aforementioned therapeutic stem cells and biomaterials to bolster the tissue's reparative capacity. Read More

Mesenchymal Stem Cells (MSCs) are adult stem cells; isolated from various body parts including bone marrow, adipose tissue and dental tissue, have been characterized well and used in regenerative medicine applications. The promising potential of MSCs makes them great candidates in many disorders. It has been well known in the literature that MSCs interact with cancer cells and regulate the carcinogenesis process at different stages. Read More

The role of pericytes seems to extend beyond their known function in angiogenesis, fibrosis and wound healing, blood-brain barrier maintenance, and blood flow regulation. More and more data are currently accumulating indicating that pericytes, uniquely positioned at the interface between blood and parenchyma, secrete a large plethora of different molecules in response to microenvironmental changes. Their secretome is tissue-specific and stimulus-specific and includes pro- and anti-inflammatory factors, growth factors, and extracellular matrix as well as microvesicles suggesting the important role of pericytes in the regulation of immune response and immune evasion of tumors. Read More

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Pericytes have crucial roles in blood-brain barrier function, blood vessel function/stability, angiogenesis, endothelial cell proliferation/differentiation, wound healing, and hematopoietic stem cells maintenance. They can be isolated from fetal and adult tissues and have multipotential differentiation capacity as mesenchymal stem cells (MSCs). All of these properties make pericytes as preferred cells in the field of tissue engineering. Read More

Pericytes wrap blood microvessels and are believed to play important roles in vascular morphogenesis, maturation, and stability. In addition, pericytes have emerged as candidates for targeting cancer growth and for wound healing. In order to model these processes and test new therapies, it is desirable to have a reliable, scalable source of pericytes. Read More

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Microcirculation is the generic name for the finest level of the circulatory system and consists of arteriolar and venular networks located upstream and downstream of capillaries, respectively. Anatomically arterioles are surrounded by a monolayer of spindle-shaped smooth muscle cells (myocytes), while terminal branches of precapillary arterioles, capillaries and all sections of postcapillary venules are surrounded by a monolayer of morphologically different perivascular cells (pericytes). Pericytes are essential components of the microvascular vessel wall. Read More

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Division of Developmental Biology, The Roslin Institute, University of Edinburgh, Edinburgh, UK.

Although pericytes have long been known for their roles in blood vessel regulation, it was not until a decade ago that their tissue regeneration potential began to be considered, after studies showed that pericytes were the in vivo counterparts of mesenchymal stem/stromal cells (MSCs). The prospective isolation and culture expansion of pericytes brought great excitement as it opened the way to the therapeutic use of well-defined cell populations with known regenerative potential to overcome concerns associated with the use of traditional MSC preparations. Studies first in humans and later in the horse and other domestic species showed that indeed cultured pericytes had key characteristics of MSCs, namely, their immunophenotype and the abilities to grow clonally and to differentiate into mature mesenchymal cells both in vitro and vivo. Read More

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Department of Neurology, School of Medicine, Wayne State University, Detroit, MI, USA.

The microvascular pericyte was identified in 1873 by the French scientist Charles Benjamin Rouget and originally called the Rouget cell (Rouget.Sciences 88:916-8, 1879). However, it was not until the early 1900s that Rouget's work was confirmed, and the Rouget cell renamed the pericyte by virtue of its peri-endothelial location (Dore. Read More

The zebrafish is an outstanding model for studying vascular biology in vivo. Pericytes and vascular smooth muscle cells can be imaged as they associate with vessels and provide stability and integrity to the vasculature. In zebrafish, pericytes associate with the cerebral and trunk vasculature on the second day of development, as assayed by pdgfrβ and notch3 markers. Read More

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Studies of pericytes have been retarded by the lack of appropriate markers for identification of these perivascular mural cells. Use of antibodies against the NG2 proteoglycan as a pericyte marker has greatly facilitated recent studies of pericytes, emphasizing the intimate spatial relationship between pericytes and endothelial cells, allowing more accurate quantification of pericyte/endothelial cell ratios in different vascular beds, and revealing the participation of pericytes throughout all stages of blood vessel formation. The functional importance of NG2 in pericyte biology has been established via NG2 knockdown (in vitro) and knockout (in vivo) strategies that reveal significant deficits in blood vessel formation when NG2 is absent from pericytes. Read More

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In the nineteenth century, a French researcher, Charles-Marie Benjamin Rouget, revealed a population of contractile cells associated with small blood vessels, which were initially named after him as the Rouget cells. In the twentieth century, a German scientist, Karl Wilhelm Zimmermann, called these cells "pericytes" due to their anatomical position located in a perivascular position. The word pericyte was derived from "peri" meaning "around" and "cyte" from the word "kytos" (cell), illustrating a cell encircling a blood vessel. Read More

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Cancer therapies are toxic. Newer oncological treatments such as immunotherapy produce unconventional adverse events that are collectively referred to as immune-related adverse events (irAEs). These irAEs are clinician-rated and typically reported via tabulation of adverse events from the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). Read More

Immune checkpoint inhibitors (ICIs) have shown significant benefit in cancer patients, but are associated with immune-related adverse events (irAEs), that can affect the gastrointestinal tract resulting in diarrhea and colitis. IrAEs range from mild self-limiting to severe life-threatening disease, which potentially limit the use of these medications. Diagnosis of ICI-induced colitis is based on clinical symptoms, physical examination, stool tests, endoscopic evaluation, and/or imaging. Read More

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Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major challenge in the treatment of cancer patients. Pneumonitis is a rare immune-related adverse event that presents in distinct patterns. Read More

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The novelty of immune checkpoint inhibitors has only recently led to the characterization of cutaneous adverse events (AEs). This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat. Pruritus and rash are among the top five immune-related AEs reported in clinical trials for this class of therapy. Read More

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In the past few years, our improved understanding of the pathogenesis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) has led to remarkable advances in the development of novel therapeutic approaches for these diseases. This chapter summarizes the available clinical data with immune-based therapeutic modalities in AML and MDS, focusing on monoclonal antibodies, T cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD-1/PD-L1 or CTLA4. Numerous clinical trials are currently ongoing in patients with AML and MDS, both in the frontline and relapsed refractory setting. Read More

The management of Non-Small Cell Lung Cancer (NSCLC) has changed dramatically in the last 10 years with an increase in the understanding of the biology and with the development of new and multiple treatments. Chemotherapy being the first systemic treatment used in the setting of advanced disease, proving benefit for patients over palliative care. With the identification of oncogenic drivers, innovative targeted therapies were developed and tested, leading to important changes in the management of certain patients and giving to some of them the possibility to be treated in first line with oral inhibitors. Read More

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While melanoma is less common than some other skin cancers, it is responsible for nearly 10,000 deaths in the USA each year alone. For many decades, very limited treatment options were available for patients with metastatic melanoma. However, recent breakthroughs have brought new hopes for patients and providers. Read More

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Tumor exists as a complex network of structures with an ability to evolve and evade the host immune surveillance mechanism. The immune milieu which includes macrophages, dendritic cells, natural killer cells, neutrophils, mast cells, B cells, and T cells are found in the core, the invasive margin, or the adjacent stromal or lymphoid component of the tumor. The immune infiltrate is heterogeneous and varies within a patient and between patients of the same tumor histology. Read More

Sports injuries diagnosis, prevention, and treatment are the most important issues of sports medicine. Fortunately, sports injuries are often treated effectively, and people with damage recover and return to the sport in a satisfactory condition. Meanwhile, many sports injuries and complications can be prevented. Read More

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Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland.

Renal perfusion, which depends on cardiac function, is a factor conditioning the work of kidneys. The objective of the study was to assess the influence of cardiac function, including left ventricular contractility and relaxation, on renal cortical perfusion in patients with hypertension and chronic kidney disease treated pharmacologically. There were 63 patients (7 F and 56 M; aged 56 ± 14) with hypertension and stable chronic kidney disease enrolled into the study. Read More

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Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.

The integrity of cellular membranes is maintained not only by structural phospholipids such as phosphatidylcholine and phosphatidylethanolamine, but also by regulatory phospholipids, phosphatidylinositol phosphates (phosphoinositides). Although phosphoinositides constitute minor membrane phospholipids, they exert a wide variety of regulatory functions in all eukaryotic cells. They act as key markers of membrane surfaces that determine the biological integrity of cellular compartments to recruit various phosphoinositide-binding proteins. Read More

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Department of Biometry, Jozef Pilsudski University of Physical Education in Warsaw, Warsaw, Poland.

The maximum rate of O uptake (V̇Omax) is one of the most important positive indicators of health. While the V̇Omax decreases with age, reducing the capacity for physical effort, it can be considerably upregulated through optimal environmental interventions, including systematic physical activity. This study seeks to determine variations in the cardiorespiratory function, estimated from the level of V̇Omax, in 798 employed men aged 20-59, according to biological (age, physical activity, body mass index (BMI), and limb muscle strength and agility) and social (place of residence, education, occupation, economic status, and smoking) predictors. Read More

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Department of Plant Pathology and Nebraska Center for Virology, University of Nebraska, Lincoln, NE, USA.

The capsid of Paramecium bursaria chlorella virus (PBCV-1) contains a heavily glycosylated major capsid protein, Vp54. The capsid protein contains four glycans, each N-linked to Asn. The glycan structures are unusual in many aspects: (1) they are attached by a β-glucose linkage, which is rare in nature; (2) they are highly branched and consist of 8-10 neutral monosaccharides; (3) all four glycoforms contain a dimethylated rhamnose as the capping residue of the main chain, a hyper-branched fucose residue and two rhamnose residues ''with opposite absolute configurations; (4) the four glycoforms differ by the nonstoichiometric presence of two monosaccharides, L-arabinose and D-mannose ; (5) the N-glycans from all of the chloroviruses have a strictly conserved core structure; and (6) these glycans do not resemble any structures previously reported in the three domains of life. Read More

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Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.

Immunoglobulin G (IgG) is a major serum glycoprotein that exerts the role of antibody in the immune system. This multifunctional glycoprotein couples antigen recognition with a variety of effector functions promoted via interactions with various IgG-binding proteins. Given its versatile functionality, IgG has recently been used for therapeutic interventions. Read More

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Cellulose is the most abundant carbohydrate on earth and hydrolyzed by cellulases in nature. During catalysis, cellulase transfers protons to and from the oxygen atoms of the glycosidic bond and a water molecule. Since cellulose is an insoluble polymer, some kinds of cellulases, with high activity toward crystalline cellulose, move on the crystal surface with continuous hydrolysis of the molecular chain. Read More

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Glycosylation of asparagine residues is a ubiquitous protein modification. This N-glycosylation is essential in Eukaryotes, but principally nonessential in Prokaryotes (Archaea and Eubacteria), although it facilitates their survival and pathogenicity. In many reviews, Archaea have received far less attention than Eubacteria, but this review will cover the N-glycosylation in the three domains of life. Read More

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N-linked oligosaccharides attached to proteins act as tags for glycoprotein quality control, ensuring their appropriate folding and trafficking in cells. Interactions with a variety of intracellular lectins determine glycoprotein fates. Monoglucosylated glycoforms are the hallmarks of incompletely folded glycoproteins in the protein quality-control system, in which glucosidase II and UDP-glucose/glycoprotein glucosyltransferase are, respectively, responsible for glucose trimming and attachment. Read More

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Glycan-protein interactions occur at many physiological events, and the analyses are of considerable importance for understanding glycan-dependent mechanisms. Biophysical approaches including 3D structural analysis are essential for revealing glycan-protein interactions at the atomic level. The inherent diversity of glycans suits them to function as identification tags, e. Read More

Authors:

Circular-dichroism (CD) spectroscopy is a powerful tool for analyzing the structures of chiral molecules and biomolecules. The development of CD instruments using synchrotron radiation has greatly expanded the utility of this method by extending the spectra to the vacuum-ultraviolet (VUV) region below 190 nm and thereby yielding information that is unobtainable by conventional CD instruments. This technique is especially advantageous for monitoring the structure of saccharides that contain hydroxy and acetal groups with high-energy transitions in the VUV region. Read More

Authors:

Individual monosaccharides can be linked in a variety of different combinations to form complex glycoconjugates. In contrast to DNA and proteins, glycoconjugate synthesis does not follow any template but is the consequence of the concerted action of various enzymes such as transferases and glycosidases . Thus, tools for glycoconjugate sequencing need to differentiate individual monosaccharide identity, linkage and anomericity to investigate and understand glycoconjugate function. Read More

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Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used for two decades to profile the glycan constituents of biological samples. An adaptation of the method to tissues, MALDI mass spectrometry imaging (MALDI-MSI), allows high-throughput spatial profiling of hundreds to thousands of molecules within a single thin tissue section. The ability to profile N-glycans within tissues using MALDI-MSI is a recently developed method that allows identification and localization of 40 or more N-glycans. Read More

Ganglioside s are involved in a variety of physiological roles and particularly in the formation and function of lipid rafts in cell membranes. However, the dynamic behaviors of gangliosides have not been investigated in living cells owing to the lack of fluorescent probes that behave like their parental molecules. This has recently been resolved by developing new fluorescent ganglioside analogues that act similarly to their parental molecules, synthesized by only chemical methods. Read More

Authors:

Densely packed carbohydrate clusters on cell surfaces play essential roles in varieties of bioprocesses. Little information has been, however, accumulated so far concerning their structural/functional details. In this chapter, we discuss artificial systems to investigate carbohydrate-carbohydrate interactions within/between the carbohydrate cluster(s). Read More

Authors:

This chapter describes the folding of synthetic homogeneous glycosylpolypeptides into glycoproteins depending on the position and number of glycosylation sites and oligosaccharide structures. To evaluate the role of oligosaccharides in protein folding, we synthesized small glycoprotein models, homogeneous misfolded glycoproteins, and erythropoietins. In addition to these chemical syntheses, this chapter introduces a unique method for N-labeling of synthetic glycoproteins to enable structural analysis. Read More

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W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, Piscataway, NJ, USA.

Discovered nearly 10 years ago by Professor Mari Dezawa and her colleagues, Muse cells are entering clinical trials faster than any other stem cell for three reasons. First, Muse cells have multiple fail-safe mechanisms to keep themselves from growing out of control and do not form tumors. In contrast, embryonic stem cells and induced pluripotent stem cells form tumors and must be differentiated before transplantation. Read More

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Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Among many kinds of somatic stem cells, hematopoietic stem cells are the cells that have been successfully applied to treating leukemia patients as forms of bone marrow and cord blood transplantation. Mesenchymal stem cells, collectable from several sources including the bone marrow and adipose tissue, are also widely applied to clinical trials for their easy accessibility and low risks of tumorigenesis, while their outcomes were shown to be not clinically relevant in several target diseases. The most important issue for the stem cells is whether the cells are safe and effective for curing diseases. Read More

Ischemia-reperfusion injury (IRI) is one of the main causes of primary graft dysfunction that accounts for 25% of mortality after lung transplantation. Disruption of blood supply and subsequent reperfusion result in organ damage with activating innate and adaptive immune response, leading to inflammatory insults. The IRI after lung transplantation is primarily manifested by permeability pulmonary edema on the basis of pulmonary vascular endothelial cell injury as seen in acute respiratory distress syndrome (ARDS). Read More

Authors:

Division of Cardiovascular Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

The aorta is a well-organized, multilayered structure comprising several cell types, namely, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and fibroblasts, as well as an extracellular matrix (ECM), which includes elastic and collagen fibers. Aortic aneurysms (AAs) are defined as progressive enlargements of the aorta that carries an incremental risk of rupture as the diameter increases over time. The destruction of the aortic wall tissue is triggered by atherosclerosis, inflammation, and oxidative stress, leading to the activation of matrix metalloproteinases (MMPs), and inflammatory cytokines and chemokines, resulting in the loss of the structural back bone of VSMCs, ECM, and ECs. Read More

Authors:

Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.

The skin composes physiological and chemical barrier and renews skin component cells throughout the human life. Melanocytes locate in the basal layer of the epidermis and produce melanin to protect the skin from ultraviolet. Melanin plays key roles in determining human skin and hair color. Read More

Authors:

Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Liver diseases account for one of the leading causes of deaths in global health care. Furthermore, chronic liver failure such as liver cirrhosis is, namely, responsible for these fatal conditions. However, only liver transplantation is an established treatment for this end-stage condition, although the availability of this salvage treatment option is quite limited. Read More

Authors:

Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.

Cellular compensation from extrahepatic resources is expected to improve the prognosis of liver diseases. Currently, liver dysfunction is treated by a variety of modalities including drugs, cytokines, vascular interventions, energy devices, surgery, and liver transplantation; however, in recent years there have been few significant advancements in treatment efficacy. A next-generation therapeutic strategy for liver disease, cellular compensatory therapy (i. Read More

Authors:

Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.

Multilineage-differentiating stress enduring (Muse) cells are one of the most promising donor cells for cell therapy against ischemic stroke, because they can differentiate into any type of cells constructing the central nervous system (CNS), including the neurons. They can easily be isolated from the bone marrow stromal cells (BMSCs), which may also contribute to functional recovery after ischemic stroke as donor cells. In this chapter, we concisely review their biological features and then future perspective of Muse cell transplantation for ischemic stroke. Read More